Trial Outcomes & Findings for A Study of Intravenous Mircera in Dialysis Patients With Chronic Renal Disease and Anemia. (NCT NCT00576303)

NCT ID: NCT00576303

Last Updated: 2016-05-26

Results Overview

All mean Hb values recorded during the evaluation period were calculated and subtracted from the mean baseline Hb value for each participant. The percentage of participants maintaining their mean Hemoglobin (Hb) concentration within +/- 1 gram/deciliter (g/dL) of their reference Hb and between 10.5 -12.5 g/dL is presented during the EEP. The EEP is defined as Week 16 to Week 24

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 200 participants
• Primary outcome timeframe: EEP (Week 16 to Week 24)
• Results posted on: 2016-05-26

Participant Flow

A total of 241 participants were recruited across 19 centers in Russia. The study was conducted from 29 Apr 2008 to 09 Jun 2010.

Of the 241 screened participants, 200 participants received the study drug and 41 participants were early withdrawals during the stability verification period (SVP)

Participant milestones

Measure	RO0503821 (1x/4 Weeks) Eligible participants started RO0503821 (Continuous Erythropoietin Receptor Activator \[C.E.R.A\]) intravenously, at a dose of 120, 200 or 360 microgram (µg) every four weeks. The dose of C.E.R.A was based on the erythropoiesis stimulating agents (ESA) like epoetin alfa or beta dose of\<8000, 8000-16000, or \>16000 international units (IU)/week, administered during the stability verification period (SVP) of 4 weeks. The SVP period was followed by dose titration period (DTP) of 16 weeks, efficacy evaluation period (EEP) of 8 weeks and long term safety period (LTSP) of 28 weeks
Dose Titration Period STARTED	200
Dose Titration Period COMPLETED	183
Dose Titration Period NOT COMPLETED	17
Efficacy Evaluation Period STARTED	183
Efficacy Evaluation Period COMPLETED	178
Efficacy Evaluation Period NOT COMPLETED	5
Long Term Safety Period STARTED	178
Long Term Safety Period COMPLETED	162
Long Term Safety Period NOT COMPLETED	16

Reasons for withdrawal

Measure	RO0503821 (1x/4 Weeks) Eligible participants started RO0503821 (Continuous Erythropoietin Receptor Activator \[C.E.R.A\]) intravenously, at a dose of 120, 200 or 360 microgram (µg) every four weeks. The dose of C.E.R.A was based on the erythropoiesis stimulating agents (ESA) like epoetin alfa or beta dose of\<8000, 8000-16000, or \>16000 international units (IU)/week, administered during the stability verification period (SVP) of 4 weeks. The SVP period was followed by dose titration period (DTP) of 16 weeks, efficacy evaluation period (EEP) of 8 weeks and long term safety period (LTSP) of 28 weeks
Dose Titration Period Early withdrawal	17
Efficacy Evaluation Period Early withdrawal	5
Long Term Safety Period Early withdrawal	16

Baseline Characteristics

A Study of Intravenous Mircera in Dialysis Patients With Chronic Renal Disease and Anemia.

Baseline characteristics by cohort

Measure	RO0503821 (1x/4 Weeks) n=200 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Age, Continuous	51.0 years STANDARD_DEVIATION 12.98 • n=5 Participants
Sex: Female, Male Female	91 Participants n=5 Participants
Sex: Female, Male Male	109 Participants n=5 Participants

PRIMARY outcome

Timeframe: EEP (Week 16 to Week 24)

Population: Per protocol (PP) population included participants except who didn't meet inclusion criterion relative to consent, stable baseline Hb values, iron status, epoetin maintenance, and who met exclusion criterion of hemoglobinopathies/hemolysis, bleeding, \>3 recorded Hb, missing drug administration, other ESA, blood transfusion during the DTP or EEP.

All mean Hb values recorded during the evaluation period were calculated and subtracted from the mean baseline Hb value for each participant. The percentage of participants maintaining their mean Hemoglobin (Hb) concentration within +/- 1 gram/deciliter (g/dL) of their reference Hb and between 10.5 -12.5 g/dL is presented during the EEP. The EEP is defined as Week 16 to Week 24

Outcome measures

Measure	RO0503821 (1x/4 Weeks) n=145 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Percentage of Participants Maintaining Average Hemoglobin Concentration Within +\- 1 Gram/Deciliter of Their Reference Hb and Between 10.5 and 12.5 Gram/Deciliter During EEP	54.5 percentage of participants Interval 46.0 to 62.8

SECONDARY outcome

Timeframe: Baseline (Week -4 to Week -1), EEP (Week 16 to Week 24)

Population: The Intent-to-Treat (ITT) population included all the participants who received at least one dose of C.E.R.A. and for whom data for at least one follow-up variable is available.

A time adjusted mean change in Hb concentration was calculated using an area under the curve approach, for both periods separately. Change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the calculated average baseline Hb value from the average evaluation period Hb value. All blood samples for Hb measurements were taken prior to study drug administration. Analysis used last observation carried forward (LOCF) for missing Hb values to correct for the impact of early dropouts. The baseline period is defined as Week -4 to Week -1. The EEP is defined as Week 16 to Week 24

Outcome measures

Measure	RO0503821 (1x/4 Weeks) n=199 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Mean Change in Hb Concentration From Baseline to the EEP	0.19 g/dL Standard Deviation 1.21

SECONDARY outcome

Timeframe: EEP (Week 16 to Week 24)

Population: The ITT population included all the participants who received at least one dose of C.E.R.A. and for whom data for at least one follow-up variable is available.

All mean Hb values recorded during the EEP were calculated. The percentage of participants maintaining their average Hb concentration within the targeted range 10.5-12.5 g/dL during the EEP were reported. The EEP is defined as Week 16 to Week 24

Outcome measures

Measure	RO0503821 (1x/4 Weeks) n=199 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Percentage of Participants Maintaining Average Hb Concentration Within Target Range of 10.5-12.5 g/dL Throughout the EEP	63.8 percentage of participants Interval 56.7 to 70.5

SECONDARY outcome

Timeframe: EEP (Week 16 to Week 24)

Population: The ITT population included all the participants who received at least one dose of C.E.R.A. and for whom data for at least one follow-up variable is available. Of the 199 participants, analysis was conducted on 184 participants, as 15 participants did not maintain their hemoglobin, within range of 10.5-12.5 g/dL during the EEP.

The mean number of days the participant spent within the Hb range 10.5-12.5 g/dL during the EEP was reported. The EEP is defined as Week 16 to Week 24

Outcome measures

Measure	RO0503821 (1x/4 Weeks) n=184 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Mean Number of Days Spent Within Hb Range of 10.5-12.5 g/dL During the EEP	34.7 number of days Standard Deviation 18.42

SECONDARY outcome

Timeframe: DTP (Week 1 to Week 16), EEP (Week 16 to Week 24) and LTSP (Week 24 to Week 44)

Population: The ITT population included all the participants who received at least one dose of C.E.R.A. and for whom data for at least one follow-up variable is available. . Data for the participants present at the time of assessment was used for analysis i.e. for DTP- 199, EEP-183, LTSP-178 respectively.

The number of participants who required dose adjustments of C.E.R.A were categorized as; 1. No dose change; 2. Any dose change: a. Dose increase only; b. Dose decrease only; c. Dose increase and increase; 3. Only one dose, all of which were recorded during DTP, EEP and LTSP. DTP is defined as Week 1 to Week 16, EEP is defined as Week 16 to Week 24 and LTSP is defined as Week 24 to Week 44

Outcome measures

Measure	RO0503821 (1x/4 Weeks) n=199 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP DTP, No dose change	50 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP DTP, Dose increase only	37 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP DTP, Dose decrease only	68 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP DTP, Dose decrease and increase	41 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP DTP, Only one dose	3 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP EEP, No dose change	81 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP EEP, Dose increase only	46 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP EEP, Dose decrease only	42 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP EEP, Dose decrease and increase	12 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP EEP, Only one dose	2 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP LTSP, No dose change	39 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP LTSP, Dose increase only	41 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP LTSP, Dose decrease only	55 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP LTSP, Dose decrease and increase	40 number of participants
Number of Participants Requiring Any Dose Adjustment During the DTP, EEP, and LTSP LTSP, Only one dose	3 number of participants

SECONDARY outcome

Timeframe: Up to 3 years

Population: The safety population was defined as all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not.

The number of participants who underwent red blood cell transfusion was reported

Outcome measures

Measure	RO0503821 (1x/4 Weeks) n=200 Participants Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Number of Participants With Red Blood Cell Transfusion	5 number of participants

Adverse Events

RO0503821 (1x/4 Weeks)

Serious events: 45 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Measure	RO0503821 (1x/4 Weeks) n=200 participants at risk Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Blood and lymphatic system disorders Anaemia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Acute myocardial infarction	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Angina pectoris	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Cardiac failure acute	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Myocardial infarction	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Myocardial ischaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Tachyarrhythmia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Abdominal hernia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Duodenal ulcer	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Inguinal hernia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Pancreatitis chronic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Peritonitis	2.0% 4/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Death	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Device dislocation	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Ill-defined disorder	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Hepatobiliary disorders Cholecystitis acute	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Hepatobiliary disorders Cholestasis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Hepatobiliary disorders Jaundice cholestatic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Ear infection	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Hepatitis B	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Lobar pneumonia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Orchitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pneumonia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pyelonephritis chronic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pyonephrosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Renal cyst infection	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Sepsis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Arteriovenous fistula aneurysm	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	7.0% 14/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Peritoneal dialysis complication	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Traumatic haematoma	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Fluid retention	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Glucose tolerance impaired	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Hyperkalaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Diabetic coma	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Ischaemic stroke	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Loss of consciousness	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Sciatica	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Transient ischaemic attack	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Psychiatric disorders Depression	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Reproductive system and breast disorders Metrorrhagia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Hypotension	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Thrombosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.

Other adverse events

Measure	RO0503821 (1x/4 Weeks) n=200 participants at risk Eligible participants started RO0503821 (C.E.R.A) intravenously, at a dose of 120, 200 or 360 µg every four weeks. The dose of C.E.R.A was based on the ESA like epoetin alfa or beta dose of \<8000, 8000-16000, or \>16000 IU/week, administered during the SVP of 4 weeks. The SVP was followed by DTP of 16 weeks, EEP of 8 weeks and LTSP of 28 weeks
Blood and lymphatic system disorders Anaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Blood and lymphatic system disorders Thrombocytopenia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Atrial fibrillation	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Bradycardia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Bundle branch block left	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Conduction disorder	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Extrasystoles	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Cardiac disorders Ventricular arrhythmia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Eye disorders Cataract	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Eye disorders Conjunctival haemorrhage	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Eye disorders Glaucoma	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Eye disorders Myopia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Eye disorders Retinopathy hypertensive	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Eye disorders Visual impairment	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Duodenal ulcer	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Dyspepsia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Erosive oesophagitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastric ulcer	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastritis	2.5% 5/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastritis atrophic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastritis erosive	2.0% 4/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastroduodenitis	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Gastrooesophageal sphincter insufficiency	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Haemorrhagic erosive gastritis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Haemorrhoids	2.0% 4/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Hiatus hernia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Melaena	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Nausea	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Pancreatitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Pancreatitis acute	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Periodontitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Gastrointestinal disorders Reflux oesophagitis	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Asthenia	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Chest pain	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Hyperthermia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Ill-defined disorder	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
General disorders Pyrexia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Hepatobiliary disorders Cholecystitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Hepatobiliary disorders Cholecystitis chronic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Hepatobiliary disorders Hepatic cirrhosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Acute sinusitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Bronchitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Hepatitis B	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Hepatitis C	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pneumonia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Postoperative wound infection	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pulpitis dental	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pyelonephritis acute	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pyelonephritis chronic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Pyonephrosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Respiratory tract infection	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Respiratory tract infection viral	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Rhinitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Sinusitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Tracheitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Tracheobronchitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Infections and infestations Viral hepatitis carrier	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Anaemia postoperative	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Arteriovenous fistula site haematoma	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Contusion	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Humerus fracture	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Poisoning	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Post procedural fistula	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Procedural hypertension	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Procedural hypotension	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Scapula fracture	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Injury, poisoning and procedural complications Vascular access complication	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Investigations Haemoglobin decreased	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Fluid retention	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Hypercholesterolaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Hyperkalaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Metabolic acidosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Metabolism and nutrition disorders Polydipsia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Arthralgia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Arthritis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Back pain	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Bursitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Muscle spasms	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Osteoarthritis	2.0% 4/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Periostitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Musculoskeletal and connective tissue disorders Synovitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign breast neoplasm	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Carpal tunnel syndrome	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Diabetic neuropathy	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Dizziness	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Headache	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Hypotonia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Intercostal neuralgia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Intracranial aneurysm	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Polyneuropathy	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Radiculitis cervical	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Radiculitis lumbosacral	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Nervous system disorders Sciatica	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Psychiatric disorders Insomnia	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Renal and urinary disorders Calculus urinary	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Renal and urinary disorders Cystitis noninfective	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Renal and urinary disorders Renal colic	1.0% 2/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Renal and urinary disorders Renal cyst	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Reproductive system and breast disorders Ovarian cyst	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Reproductive system and breast disorders Prostatitis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Skin and subcutaneous tissue disorders Pruritus	1.5% 3/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Skin and subcutaneous tissue disorders Purpura	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Aortic arteriosclerosis	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Haemorrhage	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Hypertension	8.0% 16/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Ischaemia	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.
Vascular disorders Post thrombotic syndrome	0.50% 1/200 • Up to 3 years Serious adverse events and non-serious adverse events are reported in the safety population.

Additional Information

Name/Official Title:Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: global.trial_information@roche.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER